Abstract

Protozoan parasites are microorganisms that live and feed at the expense of a host. Parasites can cause diseases in humans
and are worldwide distributed, causing high morbidity and mortality. This article describes the most important defence mechanisms
against protozoan parasites of clinical relevance (Plasmodium spp., Leishmania spp., Toxoplasma gondii, Trypanosoma cruzi, Entamoeba histolytica and Giardia lamblia). Protozoans exhibit a high heterogeneity in morphologies and antigenic expression, which is reflected in the different immune
responses induced during the infection process. The first line of defence is the mechanisms of the innate immune response
as physical and chemical barriers. However, in most cases, the adaptive humoural and cellular responses are implicated in
controlling the infection. On the other hand, parasites have developed mechanisms to evade the immune response, hindering
the development of vaccines, which offers a broad spectrum of protection among species.

Key Concepts

Parasitosis comprises a set of very diverse diseases, caused by different types of parasitic microorganisms.

Protozoan infections can be acquired either through direct contact or through vectors.

Malaria is the deadliest protozoan infection worldwide.

The immune response is divided into two branches: innate and adaptive immunity.

Protozoan parasites have developed strategies to evade the immune response.

To date, there has been an imminent necessity to develop efficient vaccines against main protozoan infections.

Figure 1.Intracellular protozoans activating different pathways of the immune response. Cells such as neutrophils, macrophages and epithelial cells (EC) participate in the innate immunity. These cells can produce reactive oxygen species (ROS, nitric oxide (NO) and cytokines such as IFN‐γ (gamma interferon) and TNF‐α (tumour necrosis factor alpha) to control the infection). Adaptive immunity is mediated by specific lymphocytes (T and B cells). T cells release cytotoxic proteins and cytokines for the activation of immune cells and B cells produce specific antibodies. Dendritic cells (DCs) and infected cells can present protozoan antigens to CD8‐positive T cells by the major histocompatibility complex class I (MHC I). The activated CD8‐positive T cells secrete cytokines such as TNF‐α to mediate the killing of infected cells. The humoural immunity provided by antibodies can be an effector in the extracellular stage of the protozoan, and B cells can intervene in the maturation of different Th cell subsets that are implicated in most intracellular parasite infections. *Some protozoans such as Toxoplasma gondii and Trypanosoma cruzi can invade different organs, depending on infection site different mechanisms of the immune response may be involved.

Figure 2.The extracellular protozoans activating different pathways of the immune response. The infection sites of Giardia lamblia and Entamoeba histolytica are in small and large gut, respectively. The physical barriers such as mucous membranes, stomach pH and biological peristalsis can control the infection. Owing to that Giardia is a noninfiltrative parasite, the DCs, macrophages and M cells may be able to mobilise Giardia antigens to lamina propria and active the adaptive immune response. Also, the intestinal epithelial cells (IEC) release potent chemokines to recruit immune cells to the invasion site. Activated macrophages release TNF‐α, stimulating neutrophils and macrophages to release ROS and NO, which can kill the parasite. ROS and NO may also contribute to tissue destruction. Major histocompatibility complex class II (MHC II) is implicated in antigen presentation of extracellular protozoans. T and B cells mediate the immune response against parasites through the antibodies IgA/IgG and cytokines of different T‐cell subsets, respectively. *E. histolytica can invade intestinal and other tissues as the liver.

Figure 3.Life cycle of Plasmodium. Malaria parasite life cycle involves two hosts. During a blood meal, a malaria‐infected female mosquito (Anopheles) inoculates sporozoites (1). Sporozoites infect liver cells (2) and mature into liver schizonts (3), which rupture and release merozoites (4). Merozoites infect red blood cells (5) and differentiate into trophozoites. Ring stage trophozoites mature into erythrocytic schizont, and its rupture releases merozoites (6). Some trophozoites mature into sexual gametocytes (7). Blood‐stage merozoites and trophozoites are responsible for clinical manifestations. Gametocytes, male and female, are ingested by mosquitoes during a blood meal (8). In mosquito's stomach, male gametocytes penetrate female gametocytes generating zygotes (9). These become ookinetes (10) which invade the midgut wall of mosquito and differentiate into oocysts (11). Oocysts grow, rupture and release sporozoites (12), which make their own way to salivary glands. The life cycle ends with the inoculation of sporozoites (1) into a new human host.

Figure 4.The life cycle of T. gondii. (a) Enteric reproduction of T. gondii in cats. (1) Tachyzoites in the lumen of the intestine invade EC, here, male and female gamonts are developed. (2) Male gamonts produce microgamonts that can swim to fertilise (3) female macrogamonts and form zygotes. (4) Zygotes mature and expel unsporulated oocysts that are shed in cats faeces. (5) Unsporulated oocysts mature and give rise to sporulated oocysts containing two sporocysts with four sporozoites. (b) Schizogony of T. gondii. (6) Sporulated oocysts are ingested by humans, rodents and livestock (cats can also get infected), bradyzoites are released and rapidly disseminate in the host body and transform into tachyzoites (the same morphology as bradyzoites but with a higher rate of division). (7) Tachyzoites invade muscle or neural tissues and transform into cyst bradyzoites. (8) As well, tachyzoites can invade immune cells to form schizonts and divide until the cell explodes and more tachyzoites are released to the blood stream (9) Tachyzoites can break the placental barrier and infect foetus in pregnant women. (10) Cyst bradyzoites can infect humans and other animals if eaten (infected raw/undercooked meat) completing the life cycle.

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